TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9368	28327;28328;28329	chr2:178711134;178711133;178711132	chr2:179575861;179575860;179575859
N2AB	9051	27376;27377;27378	chr2:178711134;178711133;178711132	chr2:179575861;179575860;179575859
N2A	8124	24595;24596;24597	chr2:178711134;178711133;178711132	chr2:179575861;179575860;179575859
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-79
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2901
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/E	rs1299434800	-0.105	0.029	None	0.551	0.162	0.463243292966	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
A/E	rs1299434800	-0.105	0.029	None	0.551	0.162	0.463243292966	gnomAD-4.0.0	1.20032E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.5641	likely_pathogenic	0.5079	ambiguous	-0.756	Destabilizing	0.676	D	0.531	neutral	None	None	None	None	N
A/D	0.3144	likely_benign	0.4012	ambiguous	-0.099	Destabilizing	0.038	N	0.577	neutral	None	None	None	None	N
A/E	0.2224	likely_benign	0.2757	benign	-0.124	Destabilizing	0.029	N	0.551	neutral	None	None	None	None	N
A/F	0.3339	likely_benign	0.3382	benign	-0.631	Destabilizing	0.214	N	0.587	neutral	None	None	None	None	N
A/G	0.1625	likely_benign	0.1696	benign	-0.807	Destabilizing	None	N	0.137	neutral	None	None	None	None	N
A/H	0.5061	ambiguous	0.5412	ambiguous	-0.875	Destabilizing	0.676	D	0.565	neutral	None	None	None	None	N
A/I	0.2003	likely_benign	0.1855	benign	-0.023	Destabilizing	None	N	0.283	neutral	None	None	None	None	N
A/K	0.4519	ambiguous	0.5248	ambiguous	-0.736	Destabilizing	0.038	N	0.553	neutral	None	None	None	None	N
A/L	0.1683	likely_benign	0.1709	benign	-0.023	Destabilizing	0.006	N	0.441	neutral	None	None	None	None	N
A/M	0.2187	likely_benign	0.2109	benign	-0.159	Destabilizing	0.016	N	0.405	neutral	None	None	None	None	N
A/N	0.2943	likely_benign	0.3129	benign	-0.499	Destabilizing	0.12	N	0.601	neutral	None	None	None	None	N
A/P	0.3287	likely_benign	0.447	ambiguous	-0.157	Destabilizing	None	N	0.283	neutral	None	None	None	None	N
A/Q	0.3245	likely_benign	0.3649	ambiguous	-0.571	Destabilizing	0.214	N	0.568	neutral	None	None	None	None	N
A/R	0.3613	ambiguous	0.4271	ambiguous	-0.533	Destabilizing	0.214	N	0.571	neutral	None	None	None	None	N
A/S	0.0967	likely_benign	0.0989	benign	-0.973	Destabilizing	None	N	0.117	neutral	None	None	None	None	N
A/T	0.0895	likely_benign	0.0889	benign	-0.878	Destabilizing	0.029	N	0.499	neutral	None	None	None	None	N
A/V	0.1135	likely_benign	0.1126	benign	-0.157	Destabilizing	None	N	0.175	neutral	None	None	None	None	N
A/W	0.693	likely_pathogenic	0.7371	pathogenic	-0.951	Destabilizing	0.864	D	0.627	neutral	None	None	None	None	N
A/Y	0.4745	ambiguous	0.4971	ambiguous	-0.513	Destabilizing	0.356	N	0.583	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.